PT802183E - Agentes estrogenicos - Google Patents
Agentes estrogenicos Download PDFInfo
- Publication number
- PT802183E PT802183E PT97302576T PT97302576T PT802183E PT 802183 E PT802183 E PT 802183E PT 97302576 T PT97302576 T PT 97302576T PT 97302576 T PT97302576 T PT 97302576T PT 802183 E PT802183 E PT 802183E
- Authority
- PT
- Portugal
- Prior art keywords
- benzyl
- methyl
- pharmaceutically acceptable
- acceptable salt
- ylethoxy
- Prior art date
Links
- 239000000262 estrogen Substances 0.000 title description 24
- 150000001875 compounds Chemical class 0.000 claims description 124
- -1 cyclic alkyl ethers Chemical class 0.000 claims description 113
- 150000003839 salts Chemical class 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 79
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 61
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 54
- 238000006243 chemical reaction Methods 0.000 claims description 32
- 238000011282 treatment Methods 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 210000001519 tissue Anatomy 0.000 claims description 11
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 11
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 10
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 10
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000004951 trihalomethoxy group Chemical group 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 6
- 230000009471 action Effects 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 206010030247 Oestrogen deficiency Diseases 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 230000002357 endometrial effect Effects 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 125000005907 alkyl ester group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 4
- 150000002170 ethers Chemical class 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- SMYMDRJWEFCCCI-UHFFFAOYSA-N trichloro(trichloromethoxy)methane Chemical compound ClC(Cl)(Cl)OC(Cl)(Cl)Cl SMYMDRJWEFCCCI-UHFFFAOYSA-N 0.000 claims description 4
- WZEOZJQLTRFNCU-UHFFFAOYSA-N trifluoro(trifluoromethoxy)methane Chemical compound FC(F)(F)OC(F)(F)F WZEOZJQLTRFNCU-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000012010 growth Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 230000035755 proliferation Effects 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- DNWWBBQJWGPFNQ-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]-3-methoxyphenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CCCCCC2)C(OC)=CC=1CN(C1=CC=C(O)C=C1C=1C)C=1C1=CC=C(O)C=C1 DNWWBBQJWGPFNQ-UHFFFAOYSA-N 0.000 claims description 2
- WINHDAHOVHUMMK-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(4-ethoxyphenyl)-3-methylindol-5-ol Chemical compound C1=CC(OCC)=CC=C1C1=C(C)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCCC1 WINHDAHOVHUMMK-UHFFFAOYSA-N 0.000 claims description 2
- IWOGIWNWSAFOMC-UHFFFAOYSA-N 1-[[4-[2-(dipropylamino)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C1=CC(OCCN(CCC)CCC)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 IWOGIWNWSAFOMC-UHFFFAOYSA-N 0.000 claims description 2
- JJGBHIULHLZNIW-UHFFFAOYSA-N 1-[[4-[2-[di(propan-2-yl)amino]ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C1=CC(OCCN(C(C)C)C(C)C)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 JJGBHIULHLZNIW-UHFFFAOYSA-N 0.000 claims description 2
- IOZPLJVUDWIYIN-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)-3-methyl-5-phenylmethoxy-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indole Chemical compound C12=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C(C=2C=C3OCOC3=CC=2)N1CC(C=C1)=CC=C1OCCN1CCCCC1 IOZPLJVUDWIYIN-UHFFFAOYSA-N 0.000 claims description 2
- RLFBHJTVTVOEBB-UHFFFAOYSA-N 2-(2,4-dimethoxyphenyl)-3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound COC1=CC(OC)=CC=C1C1=C(C)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCC1 RLFBHJTVTVOEBB-UHFFFAOYSA-N 0.000 claims description 2
- DBIQTOWPZVCCTN-UHFFFAOYSA-N 2-(3-fluoro-4-hydroxyphenyl)-3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C(F)=C1 DBIQTOWPZVCCTN-UHFFFAOYSA-N 0.000 claims description 2
- LKLLLUUCQTWHTR-UHFFFAOYSA-N 2-(4-ethoxyphenyl)-3-methyl-5-phenylmethoxy-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indole Chemical compound C1=CC(OCC)=CC=C1C1=C(C)C2=CC(OCC=3C=CC=CC=3)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCC1 LKLLLUUCQTWHTR-UHFFFAOYSA-N 0.000 claims description 2
- BJBPHCBRZFMJDW-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-1-[[3-methoxy-4-(2-piperidin-1-ylethoxy)phenyl]methyl]-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CCCCC2)C(OC)=CC=1CN(C1=CC=C(O)C=C1C=1C)C=1C1=CC=C(O)C=C1 BJBPHCBRZFMJDW-UHFFFAOYSA-N 0.000 claims description 2
- GZGPRSXNTFCESG-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-1-[[4-[2-(4-hydroxypiperidin-1-yl)ethoxy]phenyl]methyl]-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CCC(O)CC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 GZGPRSXNTFCESG-UHFFFAOYSA-N 0.000 claims description 2
- JICOGKJOQXTAIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)-3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 JICOGKJOQXTAIP-UHFFFAOYSA-N 0.000 claims description 2
- QFGIIRQJHPVWMH-UHFFFAOYSA-N 3-chloro-2-(4-hydroxy-2-methylphenyl)-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound CC1=CC(O)=CC=C1C1=C(Cl)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCC1 QFGIIRQJHPVWMH-UHFFFAOYSA-N 0.000 claims description 2
- RGPAIVZAKHHEOP-UHFFFAOYSA-N 3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]-2-(4-propan-2-yloxyphenyl)indol-5-ol Chemical compound C1=CC(OC(C)C)=CC=C1C1=C(C)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCC1 RGPAIVZAKHHEOP-UHFFFAOYSA-N 0.000 claims description 2
- VGEMBQMSELNKPV-UHFFFAOYSA-N 3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]-2-[4-(trifluoromethyl)phenyl]indol-5-ol Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(C(F)(F)F)C=C1 VGEMBQMSELNKPV-UHFFFAOYSA-N 0.000 claims description 2
- BQYMNRMHTXRMGR-UHFFFAOYSA-N 3-methyl-2-phenyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=CC=C1 BQYMNRMHTXRMGR-UHFFFAOYSA-N 0.000 claims description 2
- 206010065687 Bone loss Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 238000011161 development Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
- 238000004519 manufacturing process Methods 0.000 claims 4
- KCLKIZFYCJRAPF-UHFFFAOYSA-N 1-[[4-[2-(dimethylamino)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C1=CC(OCCN(C)C)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 KCLKIZFYCJRAPF-UHFFFAOYSA-N 0.000 claims 2
- 230000006806 disease prevention Effects 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- MZTIQFQXCDTRSS-UHFFFAOYSA-N 1-[[3-methoxy-4-(2-piperidin-1-ylethoxy)phenyl]methyl]-3-methyl-5-phenylmethoxy-2-(4-phenylmethoxyphenyl)indole Chemical compound C=1C=C(OCCN2CCCCC2)C(OC)=CC=1CN(C1=CC=2)C(C=3C=CC(OCC=4C=CC=CC=4)=CC=3)=C(C)C1=CC=2OCC1=CC=CC=C1 MZTIQFQXCDTRSS-UHFFFAOYSA-N 0.000 claims 1
- UMVQSSHQPMMTBP-UHFFFAOYSA-N 1-[[4-[2-(3,3-dimethylpiperidin-1-yl)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CC(C)(C)CCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UMVQSSHQPMMTBP-UHFFFAOYSA-N 0.000 claims 1
- UBAXLJGVTKWKOA-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]-2-methoxyphenyl]methyl]-3-methyl-5-phenylmethoxy-2-(4-phenylmethoxyphenyl)indole Chemical compound C=1C=C(CN2C3=CC=C(OCC=4C=CC=CC=4)C=C3C(C)=C2C=2C=CC(OCC=3C=CC=CC=3)=CC=2)C(OC)=CC=1OCCN1CCCCCC1 UBAXLJGVTKWKOA-UHFFFAOYSA-N 0.000 claims 1
- NJPDBAAROZVZIV-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(3-fluoro-4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C(F)=C1 NJPDBAAROZVZIV-UHFFFAOYSA-N 0.000 claims 1
- YHSACLNKCHFTRG-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(3-fluoro-4-phenylmethoxyphenyl)-3-methyl-5-phenylmethoxyindole Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C(C=C1F)=CC=C1OCC1=CC=CC=C1 YHSACLNKCHFTRG-UHFFFAOYSA-N 0.000 claims 1
- UAIZYXNIZSMLLX-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(3-methoxyphenyl)-3-methyl-5-phenylmethoxyindole Chemical compound COC1=CC=CC(C=2N(C3=CC=C(OCC=4C=CC=CC=4)C=C3C=2C)CC=2C=CC(OCCN3CCCCCC3)=CC=2)=C1 UAIZYXNIZSMLLX-UHFFFAOYSA-N 0.000 claims 1
- IRKOQFZQDDXINL-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(4-fluorophenyl)-3-methyl-5-phenylmethoxyindole Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C1=CC=C(F)C=C1 IRKOQFZQDDXINL-UHFFFAOYSA-N 0.000 claims 1
- SJEGCDZAEAPFLY-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-3-chloro-2-(4-hydroxyphenyl)indol-5-ol Chemical compound C1=CC(O)=CC=C1C1=C(Cl)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCCC1 SJEGCDZAEAPFLY-UHFFFAOYSA-N 0.000 claims 1
- UAESAJTZTXFJSA-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-3-chloro-5-phenylmethoxy-2-(4-phenylmethoxyphenyl)indole Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(Cl)=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 UAESAJTZTXFJSA-UHFFFAOYSA-N 0.000 claims 1
- UQPALZQYZZFISS-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-3-methyl-2-(4-propan-2-yloxyphenyl)indol-5-ol Chemical compound C1=CC(OC(C)C)=CC=C1C1=C(C)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCCC1 UQPALZQYZZFISS-UHFFFAOYSA-N 0.000 claims 1
- GLPVNLVSGIFUEL-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-3-methyl-2-phenyl-5-phenylmethoxyindole Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C1=CC=CC=C1 GLPVNLVSGIFUEL-UHFFFAOYSA-N 0.000 claims 1
- JEWIDHWDWPLMEZ-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-3-methyl-5-phenylmethoxy-2-(3-phenylmethoxyphenyl)indole Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 JEWIDHWDWPLMEZ-UHFFFAOYSA-N 0.000 claims 1
- NXAHBBRIVLXMQA-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-3-methyl-5-phenylmethoxy-2-(4-phenylmethoxyphenyl)indole Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 NXAHBBRIVLXMQA-UHFFFAOYSA-N 0.000 claims 1
- GFHFHPMSJFSCAG-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-5-hydroxy-2-(4-hydroxyphenyl)indole-3-carbonitrile Chemical compound C1=CC(O)=CC=C1C1=C(C#N)C2=CC(O)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCCC1 GFHFHPMSJFSCAG-UHFFFAOYSA-N 0.000 claims 1
- YFUDYZBTDAIZAO-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-5-methoxy-2-(4-methoxyphenyl)-3-methylindole Chemical compound C1=CC(OC)=CC=C1C1=C(C)C2=CC(OC)=CC=C2N1CC(C=C1)=CC=C1OCCN1CCCCCC1 YFUDYZBTDAIZAO-UHFFFAOYSA-N 0.000 claims 1
- ZAHXUDHYBXTZAN-UHFFFAOYSA-N 1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-5-phenylmethoxy-2-(4-phenylmethoxyphenyl)indole-3-carbonitrile Chemical compound C=1C=C(OCCN2CCCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C#N)=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 ZAHXUDHYBXTZAN-UHFFFAOYSA-N 0.000 claims 1
- QICKWGKIIULNMB-UHFFFAOYSA-N 1-[[4-[2-(dibutylamino)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C1=CC(OCCN(CCCC)CCCC)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 QICKWGKIIULNMB-UHFFFAOYSA-N 0.000 claims 1
- GKGRHVJUEMFGSD-UHFFFAOYSA-N 1-[[4-[2-(diethylamino)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C1=CC(OCCN(CC)CC)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 GKGRHVJUEMFGSD-UHFFFAOYSA-N 0.000 claims 1
- CMLYALNDSRHGPA-AQOUDTPCSA-N 1-[[4-[2-[(2r,6s)-2,6-dimethylpiperidin-1-yl]ethoxy]phenyl]methyl]-3-methyl-5-phenylmethoxy-2-(4-phenylmethoxyphenyl)indole Chemical compound C[C@H]1CCC[C@@H](C)N1CCOC(C=C1)=CC=C1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C(C=C1)=CC=C1OCC1=CC=CC=C1 CMLYALNDSRHGPA-AQOUDTPCSA-N 0.000 claims 1
- WANIEUSUVJHWKZ-SZPZYZBQSA-N 1-[[4-[2-[(2s,6r)-2,6-dimethylpiperidin-1-yl]ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C[C@H]1CCC[C@@H](C)N1CCOC(C=C1)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 WANIEUSUVJHWKZ-SZPZYZBQSA-N 0.000 claims 1
- UDYXSEQZOCRRKY-UHFFFAOYSA-N 1-[[4-[2-[butyl(methyl)amino]ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methylindol-5-ol Chemical compound C1=CC(OCCN(C)CCCC)=CC=C1CN1C2=CC=C(O)C=C2C(C)=C1C1=CC=C(O)C=C1 UDYXSEQZOCRRKY-UHFFFAOYSA-N 0.000 claims 1
- HSQRQXOVBSZAHO-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)-3-methyl-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indol-5-ol Chemical compound C12=CC=C(O)C=C2C(C)=C(C=2C=C3OCOC3=CC=2)N1CC(C=C1)=CC=C1OCCN1CCCCC1 HSQRQXOVBSZAHO-UHFFFAOYSA-N 0.000 claims 1
- NWEKYYJYBYMBJM-UHFFFAOYSA-N 2-(3-fluoro-4-phenylmethoxyphenyl)-3-methyl-5-phenylmethoxy-1-[[4-(2-piperidin-1-ylethoxy)phenyl]methyl]indole Chemical compound C=1C=C(OCCN2CCCCC2)C=CC=1CN1C2=CC=C(OCC=3C=CC=CC=3)C=C2C(C)=C1C(C=C1F)=CC=C1OCC1=CC=CC=C1 NWEKYYJYBYMBJM-UHFFFAOYSA-N 0.000 claims 1
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- AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/30—Oestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63397496A | 1996-04-19 | 1996-04-19 | |
| US08/833,271 US5998402A (en) | 1996-04-19 | 1997-04-04 | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indoles as estrogenic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT802183E true PT802183E (pt) | 2002-03-28 |
Family
ID=27092026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT97302576T PT802183E (pt) | 1996-04-19 | 1997-04-15 | Agentes estrogenicos |
Country Status (26)
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1011666A4 (en) * | 1997-04-30 | 2004-03-31 | Lilly Co Eli | ANTITHROMBOTIC AGENTS |
| DE69819539T2 (de) | 1997-05-01 | 2004-09-30 | Eli Lilly And Co., Indianapolis | Antithrombotische mittel |
| ID24568A (id) * | 1997-11-06 | 2000-07-27 | American Home Prod | Kontrasepsi oral yang mengandung anti-estrogen plus progestin |
| EP1082319B1 (en) * | 1998-05-12 | 2006-09-13 | Wyeth | Benzocarbazole and indenoindole derived estrogenic agents |
| US6069153A (en) * | 1998-05-12 | 2000-05-30 | American Home Products Corporation | Indenoindoles and benzocarbazoles as estrogenic agents |
| US6479535B1 (en) | 1998-05-15 | 2002-11-12 | Wyeth | 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indole and estrogen formulations |
| JP2002515484A (ja) * | 1998-05-15 | 2002-05-28 | アメリカン・ホーム・プロダクツ・コーポレイション | ２−フェニルインドール化合物およびエストロゲン製剤からなる組成物 |
| EE04262B1 (et) * | 1998-05-15 | 2004-04-15 | American Home Products Corporation | Östrogeeni ja 2-fenüül-1-[4-(2-aminoetoksü)bensüül]indooli ühendit sisaldav farmatseutiline kompositsioon ja produkt |
| US6465445B1 (en) | 1998-06-11 | 2002-10-15 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
| US7005428B1 (en) | 1998-06-11 | 2006-02-28 | Endorecherche, Inc. | Medical uses of a selective estrogen receptor modulator in combination with sex steroid precursors |
| ATE258934T1 (de) | 1998-10-30 | 2004-02-15 | Lilly Co Eli | Azaindol derivate und ihre verwendung als antithrombotische wirkstoffe |
| TWI220898B (en) * | 1999-03-04 | 2004-09-11 | Wyeth Corp | N-substituted indolines as estrogenic agents |
| US6358943B1 (en) | 1999-03-04 | 2002-03-19 | American Home Products Corporation | N-substituted indolines as estrogenic agents |
| US6380185B1 (en) | 1999-03-04 | 2002-04-30 | American Home Products Corporation | N-substituted benzoyl indoles as estrogenic agents |
| CN1342144A (zh) * | 1999-03-04 | 2002-03-27 | 美国家用产品公司 | 用作雌激素药物的n－取代的苯甲酰基吲哚类化合物 |
| PL354179A1 (en) * | 1999-09-13 | 2003-12-29 | Wyethwyeth | Glucopyranosides conjugates of 2-(4-hydroxy-phenyl)-1-[4-(2-amin-1-yl-ethoxy)-benzyl]-1h-indol-5-ols |
| US6380166B1 (en) | 1999-09-13 | 2002-04-30 | American Home Products Corporation | Glucopyranosides conjugates of 2-(4-hydroxy-phenyl)-3-methyl-1-[4-(2-amin-1-yl-ethoxy)-benzyl]-1H-indol-5-ols |
| CA2395730A1 (en) * | 2000-01-28 | 2001-08-02 | Endorecherche, Inc. | Selective estrogen receptor modulators in combination with estrogens |
| US20020013327A1 (en) * | 2000-04-18 | 2002-01-31 | Lee Andrew G. | Compositions and methods for treating female sexual dysfunction |
| CN1635885A (zh) * | 2000-07-06 | 2005-07-06 | 惠氏公司 | 应用取代吲哚化合物增强一氧化氮合酶活性 |
| WO2002003989A2 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted indole compounds for treating sphincter incontinence |
| WO2002003988A2 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted indole compounds for treating neuropeptide y-related conditions |
| US20020016318A1 (en) * | 2000-07-06 | 2002-02-07 | American Home Products Corporation | Methods of treating breast disorders |
| AR029538A1 (es) | 2000-07-06 | 2003-07-02 | Wyeth Corp | Composiciones farmaceuticas de agentes estrogenicos |
| EP1311293A2 (en) * | 2000-07-06 | 2003-05-21 | Wyeth | Combinations of ssri and estrogenic agents |
| AR030064A1 (es) * | 2000-07-06 | 2003-08-13 | Wyeth Corp | Metodos para inhibir los efectos uterotroficos de los agentes estrogenicos |
| EP1656938A1 (en) | 2000-07-06 | 2006-05-17 | Wyeth | Combinations of SSRI and estrogenic agents |
| WO2002003990A2 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted insole compounds for treating excessive intraocular pressure |
| WO2002003992A2 (en) * | 2000-07-06 | 2002-01-17 | Wyeth | Use of substituted indole compounds for treating prosthesis-related bone degeneration |
| EP1177787A3 (en) * | 2000-07-28 | 2003-09-10 | Pfizer Products Inc. | Use of an estrogen agonist/antagonist for treating cataracts |
| WO2002094788A1 (en) | 2001-05-22 | 2002-11-28 | Eli Lilly And Company | 2-substituted 1,2,3,4-tetrahydroquinolines and derivatives thereof, compositions and methods |
| US6962928B2 (en) | 2001-05-22 | 2005-11-08 | Eli Lilly And Company | Tetrahydroquinoline derivatives for the inhibition of osteoporosis, estrogen dependent breast cancer, endometriosis and uterine fibrosis |
| KR20050010886A (ko) * | 2002-06-13 | 2005-01-28 | 와이어쓰 | 바제독시펜 치료 방식 |
| HRP20041233A2 (en) | 2002-07-22 | 2005-02-28 | Eli Lilly And Company | Selective estrogen receptor modulators containing a phenylsulfonyl group |
| EP1577288B1 (en) | 2002-12-26 | 2014-07-23 | Eisai R&D Management Co., Ltd. | Selective estrogen receptor modulators |
| US7250440B2 (en) * | 2003-08-12 | 2007-07-31 | Wyeth | (Hydroxyphenyl)-1H-indole-3-carbaldehyde oxime derivatives as estrogenic agents |
| EP1732889A1 (en) | 2004-04-07 | 2006-12-20 | Wyeth | Crystalline polymorph of bazedoxifene acetate |
| US7683051B2 (en) | 2004-04-07 | 2010-03-23 | Wyeth | Crystalline polymorph of bazedoxifene acetate |
| CN1946689A (zh) | 2004-04-08 | 2007-04-11 | 惠氏公司 | 作为选择性雌激素受体调节剂的巴西多昔芬抗坏血酸盐 |
| BRPI0511834A (pt) | 2004-07-14 | 2008-01-08 | Ptc Therapeutics Inc | métodos por tratar hepatite c |
| US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| NZ553329A (en) | 2004-07-22 | 2010-09-30 | Ptc Therapeutics Inc | Thienopyridines for treating hepatitis C |
| EP1791826A2 (en) * | 2004-08-05 | 2007-06-06 | Wyeth | Crystalline polymorph of pipendoxifene hydrochloride monohydrate |
| RS20070166A (en) | 2004-10-20 | 2008-09-29 | Endorecherche Inc., | Sex steroid precursors alone or in combination with a selective estrogen receptor modulator... |
| FR2880625B1 (fr) * | 2005-01-07 | 2007-03-09 | Sanofi Aventis Sa | Derives de n-(heteroaryl)-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| US20100087661A1 (en) * | 2007-02-12 | 2010-04-08 | Josef Jirman | Method for the preparation of 5-benzyloxy-2-(4-benzyloxphenyl)-3-methyl-1h-indole |
| US8268806B2 (en) | 2007-08-10 | 2012-09-18 | Endorecherche, Inc. | Pharmaceutical compositions |
| CA2714494A1 (en) * | 2008-02-11 | 2009-08-20 | Wyeth Llc | Methods of preparing polymorphic form a of bazedoxifene acetate |
| HRP20150864T1 (hr) | 2008-04-16 | 2015-09-25 | Karo Bio Ab | Novi receptorski ligandi estrogena |
| CA2758109A1 (en) * | 2009-04-13 | 2010-10-21 | Sandoz Ag | Processes for the synthesis of bazedoxifene acetate and intermediates thereof |
| US20100317635A1 (en) | 2009-06-16 | 2010-12-16 | Endorecherche, Inc. | Treatment of hot flushes, vasomotor symptoms, and night sweats with sex steroid precursors in combination with selective estrogen receptor modulators |
| ITMI20091109A1 (it) * | 2009-06-23 | 2010-12-24 | Wyeth Corp | Forma polimorfa d di bazedoxifene acetato e metodi per la sua preparazione |
| KR20130031339A (ko) | 2010-06-16 | 2013-03-28 | 앙도르쉐르슈 인코포레이티드 | 에스트로겐-관련 질병의 치료 또는 예방 방법 |
| US7968732B1 (en) | 2010-09-07 | 2011-06-28 | Divi's Laboratories, Ltd. | Process for the preparation of 5-benzyloxy-2-(4-benzyloxyphenyl)-3-methyl-1H-indole |
| EP2616463A4 (en) | 2010-09-14 | 2014-01-08 | Reddys Lab Ltd Dr | PREPARATION OF CRYSTALLINE BAZEDOXIFES AND THEIR SALTS |
| US8569483B2 (en) | 2011-06-21 | 2013-10-29 | Divi's Laboratories, Ltd. | Process for the preparation of bazedoxifene acetate and intermediates thereof |
| CN102690225B (zh) * | 2012-04-11 | 2014-12-24 | 南京友杰医药科技有限公司 | 巴多昔芬的合成方法 |
| WO2014186325A1 (en) * | 2013-05-15 | 2014-11-20 | Indiana University Research And Technology Corporation | Processes and intermediates for preparing indole pharmaceuticals |
| US9744177B2 (en) | 2014-03-10 | 2017-08-29 | Endorecherche, Inc. | Treatment of male androgen deficiency symptoms or diseases with sex steroid precursor combined with SERM |
| CA2943611A1 (en) | 2014-03-28 | 2015-10-01 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| EP3233828B1 (en) * | 2014-12-18 | 2020-03-04 | F. Hoffmann-La Roche AG | Estrogen receptor modulators and uses thereof |
| KR20190110400A (ko) | 2018-03-20 | 2019-09-30 | 엠에프씨 주식회사 | 새로운 중간체를 이용한 바제독시펜의 제조방법 |
| IT201800006562A1 (it) * | 2018-06-21 | 2019-12-21 | Procedimento e intermedi utili per la preparazione di indoli | |
| IT201900001923A1 (it) | 2019-02-11 | 2020-08-11 | Erregierre Spa | Sali di bazedoxifene utili per la preparazione di bazedoxifene acetato |
| US11246874B1 (en) | 2021-04-20 | 2022-02-15 | Oxygen Biotech LLC | Treatment of COVID-19 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU385443A3 (enrdf_load_html_response) * | 1970-01-21 | 1973-05-29 | ||
| DE2557342A1 (de) * | 1975-12-19 | 1977-06-30 | Hoechst Ag | Basisch substituierte indolderivate und verfahren zu ihrer herstellung |
| US4656187A (en) * | 1981-08-03 | 1987-04-07 | Eli Lilly And Company | Treatment of mammary cancer |
| DE3232968A1 (de) * | 1981-09-10 | 1983-06-09 | Degussa Ag, 6000 Frankfurt | Neue 2-(hydroxy-phenyl)-indole und verfahren zu deren herstellung |
| CA1241660A (en) * | 1984-06-25 | 1988-09-06 | Yvan Guindon | Indole-2-alkanoic acids |
| GB8707051D0 (en) * | 1986-04-15 | 1987-04-29 | Ici America Inc | Heterocyclic carboxamides |
| DE3821148A1 (de) * | 1988-06-23 | 1989-12-28 | Erwin Von Dr Angerer | Aminoalkylindole, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
| US5395842A (en) * | 1988-10-31 | 1995-03-07 | Endorecherche Inc. | Anti-estrogenic compounds and compositions |
| GB9004301D0 (en) * | 1990-02-26 | 1990-04-18 | Fujisawa Pharmaceutical Co | Indolebutyric acid derivatives and process for preparation thereof |
| US5051442A (en) * | 1990-04-25 | 1991-09-24 | Merrell Dow Pharmaceuticals Inc. | 3-indolyl thioacetate derivatives and NMDA receptor antagonistic use thereof |
| WO1993023374A1 (en) * | 1992-05-08 | 1993-11-25 | Otsuka Pharmaceutical Factory, Inc. | Indole derivative |
| DE69422450T2 (de) * | 1993-06-29 | 2000-06-08 | Takeda Chemical Industries, Ltd. | Chinoline oder Chinazolin-Derivate und deren Verwendung zur Herstellung eines Medikaments für die Behandlung von Osteoporose |
| GB9326332D0 (en) * | 1993-12-23 | 1994-02-23 | Karo Bio | Indole derivatives |
| DE4426625A1 (de) * | 1994-07-27 | 1996-03-14 | Schering Ag | 2-Phenylindole, Verfahren zu deren Herstellung, diese enthaltende pharmazeutische Präparate sowie deren Verwendung zur Herstellung von Arzneimitteln |
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1997
- 1997-04-15 DK DK97302576T patent/DK0802183T3/da active
- 1997-04-15 PT PT97302576T patent/PT802183E/pt unknown
- 1997-04-15 AT AT97302576T patent/ATE206701T1/de active
- 1997-04-15 DE DE122009000061C patent/DE122009000061I1/de active Pending
- 1997-04-15 NZ NZ314601A patent/NZ314601A/en not_active IP Right Cessation
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- 1997-04-15 ES ES97302576T patent/ES2162198T3/es not_active Expired - Lifetime
- 1997-04-15 EP EP97302576A patent/EP0802183B1/en not_active Expired - Lifetime
- 1997-04-15 DE DE69707189T patent/DE69707189T2/de not_active Expired - Lifetime
- 1997-04-17 AU AU18920/97A patent/AU710149B2/en not_active Expired
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- 1997-04-17 UA UA97041833A patent/UA48148C2/uk unknown
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- 1997-04-18 HU HU9700777A patent/HU227077B1/hu active Protection Beyond IP Right Term
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2003
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2009
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- 2009-11-09 NO NO2009025C patent/NO2009025I2/no unknown
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